1. Field of the Invention
The invention relates to novel lactams extracted from an alcohol extract of dehulled adlay seeds and uses thereof.
2. Description of the Related Art
Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) is a grass crop and mainly planted in India, Taiwan, Japan, and China (Huang, S. L.; Chen, Y. F.; Chiang, W. Amino acids, fatty acids, and proximate composition of the seed of adlay. Food Sci. 1994, 21, 67-74). The seeds of adlay are also known as Chinese pearl barley and soft-shelled Job's tears. Adlay seeds have long been used in traditional Chinese medicine (TCM) to treat inflammation, dysfunctions of the endocrine system, warts, chapped skin, rheumatism, and neuralgia and also as a nourishing food (Li, S. C. Pen-t'sao kang mu (Systematic Pharmacopoeia); China, 1596). Dehulled adlay (DA) is believed to be beneficial to humans, and many processed products from adlay are manufactured as healthy foods or food supplements (Huang, S. L.; Chen, Y. F.; Chiang, W. Amino acids, fatty acids, and proximate composition of the seed of adlay. Food Sci. 1994, 21, 67-74). The DA is composed of about 8% bran and 92% endosperm, and previous studies showed that the adlay bran (AB) possesses anti-inflammatory, antiproliferative, and antiallergic activities better than the endosperm (Lee, M. Y.; Tsai, S. H.; Kuo, Y. H.; Chiang, W. Anti-tumor and anti-inflammatory activity of the methanol extracts from adlay bran. Food Sci. Biotechnol. 2008, 17, 1265-1271; Lee, M. Y.; Lin, H. Y.; Cheng, F.; Chiang, W. C.; Kuo, Y. H. Isolation and characterization of new lactam compounds that inhibit lung and colon cancer cells from adlay (Coix lachryma-jobi L. var. mayuen Stapf) bran. Food Chem. Toxicol. 2008, 46, 1933-1999; Chen, H. J.; Shih, C. K.; Hsu, H. Y.; Chiang, W. Mast cell dependent allergic responses are inhibited by ethanolic extract of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) testa. J. Agric. Food Chem. 2010, 58, 2596-2601).
In line with the medicinal uses of adlay, many studies have been performed to evaluate its effects. A series of studies on antitumorrelated activities of adlay seeds have been reported. Coixenolide (Tanimura, A. Studies on the anti-tumor component in the seeds of Coix lachryma-jobi L. var. ma-yuen (Roman.) Stapf. II. The structure of coixenolide. Chem. Pharm. Bull. 1961, 9, 47-53), fatty acids (Tokuda, H.; Matsumoto, T.; Konoshima, T.; Kozuka, M.; Nishino, H.; Iwashima, A. Inhibitory effects on Epstein-Barr virus activation and anti-tumor promoting activities of Coix seed. Planta Med. 1990, 56, 653-654), and a neutral lipid extract (Woo, J. H.; Li, D.; Wilsbach, K.; Orita, H.; Coulter, J.; Tully, E.; Kwin, T. K.; Xu, S.; Gabrielson, E. Coix seed extract, a commonly used treatment for cancer in China, inhibits NFκB and protein kinase C signaling. Cancer Biol. Ther. 2007, 6, 2005-2010; Yu, F.; Gao, J.; Zeng, Y.; Liu, C. X. Inhibition of Coix seed extract on fatty acid synthase, a novel target for anticancer activity. J. Ethnopharmacol. 2008, 119, 252-258; Lu, Y.; Wu, L. Q.; Dong, Q.; Li, C. S. Experimental study on the effect of Kang-Lai-Te induced apoptosis of human heptoma carcinoma cell HepG2. Hepatobiliary Pancreatic Dis. Int. 2009, 8, 267-272) have been claimed as its active components. Lee et al. reported that a methanolic extract of AB had antitumor and anti-inflammatory activities (Lee, M. Y.; Tsai, S. H.; Kuo, Y. H.; Chiang, W. Anti-tumor and anti-inflammatory activity of the methanol extracts from adlay bran. Food Sci. Biotechnol. 2008, 17, 1265-1271) and that cytotoxic lactams have been isolated (Lee, M. Y.; Lin, H. Y.; Cheng, F.; Chiang, W. C.; Kuo, Y. H. Isolation and characterization of new lactam compounds that inhibit lung and colon cancer cells from adlay (Coix lachryma-jobi L. var. mayuen Stapf) bran. Food Chem. Toxicol. 2008, 46, 1933-1999). Additionally, the ethyl acetate (EA) fraction of AB ethanolic extract (ABE-EA) is shown to suppress aberrant crypt foci (ACF) in dimethyl hydrazine (DMH)-induced colon carcinogenesis (Chung, C. P.; Hsu, H. Y.; Huang, D. W.; Hsu, H. H.; Lin, J. T.; Shih, C. K.; Chiang, W. Ethyl acetate fraction of adlay bran ethanolic extract inhibits oncogene expression and suppresses DMH-induced preneoplastic lesions of the colon in F344 rats through an anti-inflammatory pathway. J. Agric. Food Chem. 2010, 58, 7616-7623).
The modulatory effects in the endocrine system of adlay seeds have been reported (Hsia, S. M.; Yeh, C.; Kuo, Y. H.; Wang, P. S.; Chiang, W. Effects of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) hull extracts on the secretion of progesterone and estradiol in vivo and in vitro. Exp. Biol. Med. 2007, 232, 1181-1194; Hsia, S. M.; Tseng, Y. W.; Wang, S. W.; Kuo, Y. H.; Huang, D. W.; Wang, P. S.; Chiang, W. Effect of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) hull extracts on testosterone release from rat Leydig cells. Phytother. Res. 2009, 23, 687-695). Human breast cancer cells that express estrogen receptor (ER) and prostate cancer cells that express androgen receptor (AR) are closely involved with cells that secrete hormone; they are regarded as benign but possibly may turn into a malignant tumor (Ho, C. Y.; Kim, C, F.; Leung, K. N.; Fung, K. P.; Tse, T. F.; Chan, H.; Lau, C. B. Differential anti-tumor activity of Coriolus versicolor (Yunzhi) extract through p53- and/or Bcl-2-dependent apoptotic pathway in human breast cancer cells. Cancer Biol. Ther. 2005, 4, e11-e17).
Lactams have been previously reported as an antiproliferative agent for human cancer cells in some literature. Meegan et al. found that β-lactam-type molecular scaffolds inhibited breast cancer cell proliferation (Meegan, M. J.; Carr, M.; Knox, A. J. S.; Zisterer, D. M.; loyd, D. G. β-Lactam type molecular scaffolds for antiproliferative activity: Synthesis and cytotoxic effects in breast cancer cells. J. Enzyme Inhib. Med. Chem. 2008, 23, 668-685). Davis et al. isolated two caprolactams, pestalactam A and pestalactam B, that suppress MCF-7 cell growth (Davis, R. A.; Carroll, A. R.; Andrews, K. T.; Boyle, G. M.; Tran, T. L.; Healy, P. C.; Kalaitzis, J. A.; Shivas, R. G. Pestalactams A-C: Novel caprolactams from the endophytic fungus Pestalotiopsis sp. Org. Biomol. Chem. 2010, 8, 1785-1790). Hormone-dependent human breast and renal cancer cells were also founds to be inhibited by a γ-lactam-based histone deacetylase inhibitor (Kwon, H. K.; Ahn, S. H.; Park, S. H.; Park, J. H.; Park, J. W.; Kim, H. M.; Park, S. K.; Lee, K.; Lee, C. W.; Choi, E.; Han, G.; Han, J. W. A novel γ-lactam-based histone deacetylase inhibitor potently inhibits the growth of human breast and renal cancer cells. Biol. Pharm. Bull. 2009, 32, 1723-1727).
Nonetheless, the effects of AB on endocrine related cancer cells and related components of adlay bran remain unclear.